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To analyze the mechanisms of HCV drug resistance by using chimeric HCV cell culture system

Research Project

Project/Area Number 25860513
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Gastroenterology
Research InstitutionHokkaido University

Principal Investigator

SUDA Goki  北海道大学, 医学(系)研究科(研究院), 特任助教 (20447460)

Co-Investigator(Renkei-kenkyūsha) SAKAMOTO Naoya  北海道大学, 大学院医学研究科, 教授 (10334418)
Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsHCV / IFN / 薬剤耐性ウイルス / HCV
Outline of Final Research Achievements

The mechanism of HCV resistance to IFN has not been wellunderstood. We conducted homologous recombination between HCV-2b and JFH1 and ensured that the chimeric virus could be long-cultured. Then we long-cultured HCV-2b/JFH1 chimeric virus (C3) with or without IFN and compared virus kinetics between the two groups, and tried to extract IFN resistant clone. Supernatant HCV of C3 decreased immediately. However, 6 weeks after IFN treatment, replication of one C3 clone increased . Comparison of amino acid sequences revealed two sequence differences in structure region. Next we constructed these two sequence differences substituted C3 clone (IFNrC3) and compared IFN sensitivity between IFNrC3 and C3 by transfection into cells and subsequently IFN treatment. The newly constructed IFNrC3 showed resistance to IFN.
Additionally, we investigated prevalence of resistant HCV against DAA in japan by using NGS. The existence of resistant virus did not affect treatment outcome in TPV based therapy.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (19 results)

All 2015 2014 2013

All Journal Article (10 results) (of which Peer Reviewed: 6 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (9 results)

  • [Journal Article] EGFR inhibitors eliminate cancer stem-like cells in esophageal squamous cell carcinoma by suppressing epithelial-mesenchymal transition2015

    • Author(s)
      1.Fumiyuki Sato, Yoshimasa Kubota, Mitsuteru Natsuizaka, Osamu Maehara, Yutaka Hatanaka, Katsuji Marukawa, Katsumi Terashita, Goki Suda, Shunsuke Ohnishi, Yuichi Shimizu, Yoshito Komatsu, Shinya Ohashi, Shingo Kagawa, Hideaki Kinugasa, Kelly Whelan, Anil Rustgi, Hiroshi Nakagawa, and Naoya Sakamoto
    • Journal Title

      Cancer Biology & Therapy

      Volume: Epub ahead of print

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Human amnion-derived mesenchymeal stem cell transplantation ameliorates dextran sulfate sodium-induced severe colitis in rats.2015

    • Author(s)
      2.Onishi R, Ohnishi S, Higashi R, Watari M, Yamahara K, Okubo N, Nakagawa K, Katsurada T, Suda G, Natsuizaka M, Takeda H, Sakamoto N
    • Journal Title

      Cell Transplantation

      Volume: Epub ahead of print

    • NAID

      120005690898

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intratumoral artery on contrast-enhanced computed tomography imaging: differentiating intrahepatic cholangiocarcinoma from poorly differentiated hepatocellular carcinoma2015

    • Author(s)
      3.Tsunematsu S1, Chuma M, Kamiyama T, Miyamoto N, Yabusaki S, Hatanaka K, Mitsuhashi T, Kamachi H, Yokoo H, Kakisaka T, Tsuruga Y, Orimo T, Wakayama K, Ito J, Sato F, Terashita K, Nakai M, Tsukuda Y, Sho T, Suda G, Morikawa K, Natsuizaka M, Nakanishi M, Ogawa K, Taketomi A, Matsuno Y, Sakamoto N
    • Journal Title

      Abdom Imaging.

      Volume: Epub ahead of print

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Serum granulysin levels as a predictor of serious telaprevir-induced dermatological reactions.2015

    • Author(s)
      Suda G, Yamamoto Y, Nagasaka A, Furuya K, Kudo M, Chuganji Y, Tsukuda Y, Tsunematsu S, Sato F, Terasita K, Nakai M, Horimoto H, Sho T, Natsuizaka M, Ogawa K, Ohnishi S, Chuma M, Fujita Y, Abe R, Taniguchi M, Nakagawa M, Asahina Y, Sakamoto N
    • Journal Title

      Hepatol Res

      Volume: 印刷中 Issue: 8 Pages: 837-45

    • DOI

      10.1111/hepr.12421

    • NAID

      120005820706

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Heat shock factor 1 accelerates hepatocellular carcinoma development by activating nuclear factor κB/mitogen-activated protein kinase.2014

    • Author(s)
      Chuma M, Sakamoto N, Nakai A, Hige S, Nakanishi M, Natsuizaka M, Suda G, Sho T, Hatakaka K, Matsuno Y, Yokoo H, Kamiyama T, Taketomi A, Fujii G, Tashiro K, Hikiba Y, Fujimoto M, Asaka M, Maeda S
    • Journal Title

      Carcinogenesis

      Volume: Epub ahead of print Issue: 2 Pages: 272-281

    • DOI

      10.1093/carcin/bgt343

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hepatosplenic Gamma-delta T-cell Lymphoma Associated with Epstein-Barr Virus2014

    • Author(s)
      6.Seiji Tsunematsu, Mitsuteru Natsuizaka, Hiromi Fujita, Noriyuki Otsuka, Katsumi Terashita, Fumiyuki Sato, Tomoe Kobayashi, Masato Nakai, Yoko Tsukuda, Hiromasa Horimoto, Takuya Sho, Goki Suda, Mitsuru Nakanishi, Satoshi Hashino, Makoto Chuma, Naoya Sakamoto
    • Journal Title

      Intern Med

      Volume: 53(18) Pages: 2079-2082

    • NAID

      130004687645

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Telaprevir:副作用とその対策2014

    • Author(s)
      須田剛生、坂本直哉
    • Journal Title

      Internal Medicine

      Volume: 67 Pages: 855-860

    • Related Report
      2013 Research-status Report
  • [Journal Article] インターフェロン少量長期療法の実際と新薬時代における役割2014

    • Author(s)
      須田剛生、坂本直哉
    • Journal Title

      内科

      Volume: 113 Pages: 681-685

    • Related Report
      2013 Research-status Report
  • [Journal Article] C型肝炎ウイルス蛋白によるシグナル伝達制御2013

    • Author(s)
      須田剛生、坂本直哉
    • Journal Title

      分子消化器病

      Volume: 10 Pages: 68-72

    • Related Report
      2013 Research-status Report
  • [Journal Article] IL6を介したC型慢性肝炎のインターフェロン治療抵抗性機構2013

    • Author(s)
      須田剛生、坂本直哉
    • Journal Title

      消化器内科

      Volume: 56 Pages: 421-426

    • Related Report
      2013 Research-status Report
  • [Presentation] DAA併用療法におけるDAA耐性ウイルス/治療予測因子の検討2014

    • Author(s)
      須田剛生 古家乾 坂本直哉
    • Organizer
      肝臓病学会東部会
    • Place of Presentation
      京王プラザホテル (東京 新宿)
    • Year and Date
      2014-11-29
    • Related Report
      2014 Annual Research Report
  • [Presentation] C型肝炎は完治できる時代へ2014

    • Author(s)
      須田剛生
    • Organizer
      日本臨床検査医学学術集会
    • Place of Presentation
      福岡国際会議場 (福岡県 博多)
    • Year and Date
      2014-11-24
    • Related Report
      2014 Annual Research Report
  • [Presentation] Serum granulysin levels as a predictor of serious telaprevir-induced dermatological reaction2014

    • Author(s)
      Goki Suda1 ,Yoko Tsukuda1, Seiji Tsunematsu1, Fumiyuki Satou1, Katsumi Terasita1, Takuya Sho 1, Masato Nakai1, Mitsuteru Natsuizka1, Makoto Chuma 1, Naoya Sakamoto
    • Organizer
      65th. Annual Meeting of American Association for the Study of Liver Diseases
    • Place of Presentation
      Boston (USA)
    • Year and Date
      2014-11-09
    • Related Report
      2014 Annual Research Report
  • [Presentation] Analysis of First and Second Generation Protease Inhibitor Combination Therapy in Patients with Chronic Hepatitis C Virus Infection2014

    • Author(s)
      須田剛生 永坂敦 坂本直哉
    • Organizer
      日本消化器病関連学会週間
    • Place of Presentation
      神戸国際展示場 (兵庫県 神戸)
    • Year and Date
      2014-10-23
    • Related Report
      2014 Annual Research Report
  • [Presentation] C型慢性肝炎に対するDAA療法の治療予測因子・薬剤耐性ウイルスの検討2014

    • Author(s)
      須田剛生 中馬 誠 坂本直哉
    • Organizer
      肝臓病学会総会
    • Place of Presentation
      ホテルニューオータニ (東京都 千代田区)
    • Year and Date
      2014-05-29
    • Related Report
      2014 Annual Research Report
  • [Presentation] プロテアーゼ阻害剤併用療法の治療予測因子・薬剤耐性ウイルスの検討2014

    • Author(s)
      須田剛生 中馬 誠 坂本直哉
    • Organizer
      消化器病学会総会
    • Place of Presentation
      東京国際フォーラム (東京都 千代田区)
    • Year and Date
      2014-04-24
    • Related Report
      2014 Annual Research Report
  • [Presentation] Serum granulysin level is correlated with severity of telaprevir induced dermatological adverse reactions and could be a useful predictor2014

    • Author(s)
      Goki Suda , Yoshiya Yamamoto, Astusi Nagasaka, Ken Furuya, Yoko Tsukuda, Seiji Tsunematsu, Fumiyuki Satou, Katsumi Terasita, Keita Horimoto, Takuya Sh Masato Nakai, Mitsuteru Natsuizka, Makoto Chuma , Naoya Sakamoto
    • Organizer
      Asian Pacific Association for The Study of the Liver
    • Place of Presentation
      Brisbane Convention & Exhibition Centre(Brisbene), Australia
    • Related Report
      2013 Research-status Report
  • [Presentation] Establishment of Interferon resistant genotype 2b/JFH-1 chimeric Hepatitis C virus cell culture system2013

    • Author(s)
      Goki Suda, Yoko Tsukuda, Mitsuteru Natsuizaka, Makoto Chuma, Naoya Sakamoto
    • Organizer
      64th. Annual Meeting of American Association for the Study of Liver Diseases
    • Place of Presentation
      Walter E. Washington Convention Center (Wachington DC), USA
    • Related Report
      2013 Research-status Report
  • [Presentation] Telaprevir/Peg-IFN/RBV3剤併用療法の治療効果および副作用予測因子の解析2013

    • Author(s)
      須田剛生 中馬誠 坂本直哉
    • Organizer
      日本消化器病関連学会週間
    • Place of Presentation
      グランドプリンス高輪ホテル(東京)
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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